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Pediatric Pulmonology Jun 2024Elexacaftor-tezacaftor-ivacaftor (ETI) is a highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulating therapy for people with CF and at...
BACKGROUND
Elexacaftor-tezacaftor-ivacaftor (ETI) is a highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulating therapy for people with CF and at least one F508del variant. However, there is limited data about the safety and efficacy of this therapy in pediatric populations and in real-world settings. This study aimed at evaluating the effectiveness, tolerability, and safety of ETI in children with CF.
METHODS
This was a prospective observational study including all children aged 6-11 years who initiated ETI therapy between October 2022 and March 2023 at the Pediatric CF Center of Milan (Italy). Study outcomes included changes in sweat chloride concentration, FEV, LCI, body mass index (BMI), tolerance, and safety. Mean changes in study outcomes from baseline through 24 weeks were estimated using mixed-effects regression models.
RESULTS
The study included 34 children with CF (median age: 8.3 years). At Week 12, we observed an average decrease in LCI of 2.3 units (95% confidence interval [CI]: -3.1; -1.5). At Week 24, sweat chloride concentration decreased by 63 mEq/L (95% CI: -69; -58), FEV increased by 8.8 percentage point (95% CI: 3.7; 13.9) and BMI increased by 0.15 standard deviation scores (95% CI: 0.04; 0.25). Skin rashes appeared in 6 patients which spontaneously resolved within a few days. One month after treatment initiation, one patient experienced an elevation in liver function test results, which subsequently decreased during follow-up visits without necessitating discontinuation of therapy.
CONCLUSIONS
Our data indicate that ETI therapy is well tolerated by children with CF and is effective in improving signs of lung function abnormalities from early childhood.
PubMed: 38869349
DOI: 10.1002/ppul.27125 -
Cureus May 2024The diagnosis of skin lesions involving the eyes can be challenging, especially when uncommon etiologies are considered. We present a case of a 52-year-old female...
The diagnosis of skin lesions involving the eyes can be challenging, especially when uncommon etiologies are considered. We present a case of a 52-year-old female initially diagnosed with blepharoconjunctivitis but later found to have a subcutaneous heartworm infection. The patient experienced recurrent episodes of unilateral palpebral edema, pain, pruritus, and a sensation of a foreign body in her eye. Upon examination, a vermiform structure with peristaltic movements was observed, raising suspicion of subcutaneous dirofilariasis and prompting further investigations. Serological tests confirmed the presence of anti- spp. antibodies. Surgical removal of the worm led to the resolution of symptoms. This case highlights the importance of considering uncommon etiologies, such as subcutaneous heartworm infection, in patients presenting with atypical migratory skin lesions or ocular manifestations when there is no definite diagnosis and the condition does not respond to usual medical treatment.
PubMed: 38868288
DOI: 10.7759/cureus.60208 -
American Journal of Kidney Diseases :... Jun 2024Monkeypox (mpox) is an orthopoxviral zoonotic disease with a similar, but less severe, clinical presentation as smallpox. However, immunocompromised patients such as...
Monkeypox (mpox) is an orthopoxviral zoonotic disease with a similar, but less severe, clinical presentation as smallpox. However, immunocompromised patients such as solid organ transplant recipients are at higher risk of developing severe forms of the disease. Herein, we describe the case of a 43 years-old female kidney transplant recipient that manifested severe skin ulcers alongside nodular lung opacities and pleural effusion attributed directly to the Monkeypox virus. Notwithstanding the initiation of early treatment with tecovirimat, a satisfactory response was not achieved until a reduction in immunosuppression to everolimus monotherapy, coupled with the transition to cidofovir for antiviral treatment. In conclusion, mpox has the potential to produce a severe form of systemic infection in individuals who have undergone solid organ transplantation, demanding a meticulous approach involving sequential antiviral treatment and modifications to immunosuppressive regimens in order to achieve complete healing.
PubMed: 38866126
DOI: 10.1053/j.ajkd.2024.06.001 -
Journal of Cutaneous Pathology Jun 2024Human protothecosis is an uncommon infection caused by Prototheca spp that rarely infects humans.
BACKGROUND
Human protothecosis is an uncommon infection caused by Prototheca spp that rarely infects humans.
AIM
Description of a rare disease and a review of its articles.
MATERIALS AND METHODS
We reported a 24-year-old man who presented with red-brown papules and plaques on the trunk's lateral side. We reviewed the literature about disseminated protothecosis and reported our experience with a patient with protothecosis between 2021 and 2023.
RESULTS
Overall, 54 cases of disseminated protothecosis were evaluated, 39 were due to P. wickerhamii, 12 were due to P. zopfii (22.2%), and three were due to Prototheca spp. We found that males were more affected (37 cases, 68.5%) than females (16 cases, 29.6%). The mean age of patients was 39.53 ± 22.48 years. However, disseminated protothecosis can affect people of any age (1-80 years). In contrast to P. wickerhamii, which causes blood, skin, brain, and gastrointestinal tract infections, P. zopfii was mainly found in the blood (7/22) and did not have a significant difference in the mortality rate (P = 0.11).
DISCUSSION
Disseminated protothecosis is a rare disease in immunocompromised patients but is generally rarer in immunocompetent hosts. Several underlying disorders include immunocompromised patients, prolonged application of steroids, diabetes mellitus, malignancies, organ transplantation, AIDS, and surgeries. Amphotericin B has been the most effective agent for protothecosis and is reserved for visceral and disseminated infections. Regarding localized cutaneous types, excision or surgical debridement is used.
CONCLUSION
Mulberry's appearance and appropriate cultural environments are helpful in diagnosing it.
PubMed: 38863080
DOI: 10.1111/cup.14668 -
Wounds : a Compendium of Clinical... May 2024Full-thickness skin defects often are managed with split-thickness skin grafting. The wound healing process, including formation of new vessels during the healing of...
BACKGROUND
Full-thickness skin defects often are managed with split-thickness skin grafting. The wound healing process, including formation of new vessels during the healing of skin grafts, is complex.
OBJECTIVE
To evaluate the microcirculatory changes in the treated tissue after skin grafting to analyze perfusion dynamics during the wound healing process.
MATERIALS AND METHODS
Fourteen full-thickness skin defects were created on the back of 14 adult male Lewis rats. All wounds were treated with autologous split-thickness skin grafts. The perfusion dynamics were assessed for 84 days with an O2C device that combines a laser light to determine blood flow and white light to determine postcapillary SO2 and the rHb.
RESULTS
Blood flow increased for 50 days after grafting. SO2 decreased in superficial skin layers (depth of 2 mm) and increased in deep skin layers (depth of 8 mm) during the entire observation period. The rHb increased until day 10 in superficial layers and until day 20 in deep tissue layers.
CONCLUSION
The microcirculatory changes reflect the different phases of wound healing. Long after the skin transplants were macroscopically healed, alterations in microcirculation were still detected. These alterations were caused by the long-lasting changes in tissue metabolism due to the formation, conversion, and degradation of the dermal matrix and vessels during wound healing and scar formation.
Topics: Animals; Wound Healing; Microcirculation; Skin Transplantation; Rats; Male; Rats, Inbred Lew; Skin; Disease Models, Animal
PubMed: 38861214
DOI: 10.25270/wnds/23112 -
Diagnostic Cytopathology Jun 2024Kaposi sarcoma (KS) is a low-grade vascular neoplasm that can be seen in various sites, most commonly seen in skin and mucosal tissues. Cytologic features of KS have...
Kaposi sarcoma (KS) is a low-grade vascular neoplasm that can be seen in various sites, most commonly seen in skin and mucosal tissues. Cytologic features of KS have been well-documented in the literature, however, since it is rarely seen in visceral organs, it could pose significant diagnostic challenges on fine needle aspiration (FNA) biopsies. We present a case of pulmonary KS diagnosed on transbronchial FNA biopsy in a 70-year-old female bilateral lung allograft recipient 11 months after transplantation. The aspirate smears showed a moderately cellular specimen containing a mixture of small, tightly cohesive clusters and loosely clustered groups of monomorphic, ovoid to spindled cells with moderate nuclear to cytoplasmic ratio. An extensive immunohistochemical panel on the concurrent core biopsy showed the tumor cells to be positive for ERG, KIT, and HHV8, confirming the diagnosis. We compared our case to previously published reports of confirmed pulmonary KS in lung allograft recipients.
PubMed: 38860692
DOI: 10.1002/dc.25368 -
International Wound Journal Jun 2024Early wound intervention and closure is critical for reducing infection and improving aesthetic and functional outcomes for patients with acute burn wounds and...
Early wound intervention and closure is critical for reducing infection and improving aesthetic and functional outcomes for patients with acute burn wounds and nonthermal full-thickness skin defects. Treatment of partial-thickness burns or full-thickness injuries with autologous skin cell suspension (ASCS) achieves robust wound closure while limiting the amount of donor skin compared with standard autografting. A Next Generation Autologous Cell Harvesting Device (NG-ACHD) was developed to standardize the preparation process for ASCS to ensure biological attributes are obtained known to correlate with well-established safety and performance data. This study compared ASCS prepared using the NG-ACHD and ACHD following the manufacturer's guidance, evaluating cellular yields, viability, apoptotic activity, aggregates, phenotypes and functional capacity. Non-inferiority was established for all biological attributes tested and comparable healing trajectories were demonstrated using an in vitro skin regeneration model. In addition to standardization, the NG-ACHD also provides workflow efficiencies with the potential to decrease training requirements and increase the ease of incorporation and utilization of ASCS in clinical practice.
Topics: Humans; Transplantation, Autologous; Wound Healing; Burns; Regeneration; Skin Transplantation; Tissue and Organ Harvesting; Epidermal Cells; Epidermis; Male; Female
PubMed: 38860606
DOI: 10.1111/iwj.14941 -
European Review For Medical and... May 2024Recently, the infiltration of a subpopulation of cells represented by mononucleated cells extracted from peripheral blood [Peripheral Blood-Mononuclear Cells (PB-MNCs)]...
BACKGROUND
Recently, the infiltration of a subpopulation of cells represented by mononucleated cells extracted from peripheral blood [Peripheral Blood-Mononuclear Cells (PB-MNCs)] is becoming a useful technique for medical and surgical regenerative procedures. Due to the angiogenetic and regenerative properties of PB-MNCs, the infiltration of these cells is, in our opinion, a new option indicated in the treatment of pathologies characterized by tissue dystrophy, loss of vascularization, and non-healing wounds.
CASE PRESENTATION
A 25-year-old active smoker patient was diagnosed with Rhabdomyosarcoma of the anterior tibial muscle of his left leg and treated with neoadjuvant chemo- and radiotherapy (RT). After the tumor excision, the patient developed wound dehiscence with bone exposure and a perilesional radiation-induced chronic dermatitis characterized by skin dyschromia and hair thinning along the treated area. The patient underwent surgical debridement and reconstruction with autologous skin grafts and dermal substitutes, with poor outcomes due to graft failure. The patient was subsequently treated with surgical debridement and coverage with a reverse sural fascia-cutaneous flap. After 13 days, wound dehiscence was observed, and reconstruction of the dehiscent areas was performed with a split-thickness autologous skin graft with no success. After wound debridement, a new split-thickness skin graft was performed, and a concentrate of autologous PB-MNCs was injected in the flap and perilesional skin. After 14 days, graft take was reached, and improvements in perilesional tissue tropism were noted. At 2 months follow-up, the patient appeared completely healed.
CONCLUSIONS
In our opinion, the use of PB-MNCs to treat conditions characterized by tissue dystrophy, which require neoangiogenesis and cell regeneration, can be a useful and unconsidered technique that could be utilized to improve tissue tropism. Furthermore, prospective trials are necessary to validate our observations.
Topics: Humans; Male; Adult; Leukocytes, Mononuclear; Plastic Surgery Procedures; Lower Extremity; Rhabdomyosarcoma; Wound Healing
PubMed: 38856134
DOI: 10.26355/eurrev_202405_36295 -
Actas Dermo-sifiliograficas Jun 2024Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10...
Blastic plasmacytoid dendritic cell neoplasm: a single-center experience. Clinical characterization, mutational landscape, and clinical outcome of patients undergoing hematopoietic stem cell transplantation intensive therapy.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular dermal-based infiltrates of intermediate sized blasts with a grenz zone. Tumor immunophenotyping was CD4(+), CD56(+), CD123(+) and CD303(+). The most frequently mutated genes according to targeted next-generation sequencing were TET2 (3/7) and NRAS (2/7). Multiagent chemotherapy (CT) was administered as first-line therapy, and a total of 5 patients underwent allogenic hematopoietic stem cell transplantation (allo-HSCT). Better outcomes were observed in younger patients and those treated with acute lymphoblastic leukemia (ALL)-like CT followed by allo-HSCT. This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seem to have a more favorable prognosis.
PubMed: 38852841
DOI: 10.1016/j.ad.2023.09.029 -
International Immunopharmacology Jul 2024Iguratimod (IGU) is widely used in clinical practice due to its stable anti-inflammatory effects. Our previous studies have confirmed that the proportion of Th17/Treg...
BACKGROUND
Iguratimod (IGU) is widely used in clinical practice due to its stable anti-inflammatory effects. Our previous studies have confirmed that the proportion of Th17/Treg balance in patients taking IGU altered significantly. This study aims to explore the role of IGU in antibody-mediated rejection (ABMR) and its potential mechanisms.
METHODS
We conducted bioinformatics analysis of sequencing data from the GEO database to analyze the abundance of immune cell infiltration in transplanted kidney tissues. In vivo, IGU was intervened in a mice secondary skin transplantation model and a mice kidney transplantation ABMR model, and histological morphology of the grafts were examined by pathological staining, while relevant indicators were determined through qRT-PCR, immunohistochemistry, and enzyme-linked immunosorbent assay, observed T cell differentiation by flow cytometry, and preliminarily assessed the immunosuppressive effect of IGU. In vitro, we established Th17 and Treg cell induction and stimulation differentiation culture systems and added IGU for intervention to explore its effects on their differentiation.
RESULTS
Through bioinformatics analysis, we found that Th17 and Treg may play important roles in the occurrence and development of ABMR. In vivo, we found that IGU could effectively reduce the damage caused by ABMR to the grafts, alleviate the infiltration of inflammatory cells in the graft tissues, and reduce the deposition of C4d in the grafts. Moreover, it is also found that IGU regulated the differentiation of Th17 and Treg cells in the spleen and peripheral blood and reduced the expression of IL-17A in the grafts and serum. In addition, same changes were observed in the induction and differentiation culture system of Th17 and Treg cells in vitro after the addition of IGU.
CONCLUSION
IGU can inhibit the progression of ABMR by regulating the differentiation of Th17 and Treg cells, providing novel insights for optimizing clinical immunosuppressive treatment regimens.
Topics: Animals; Th17 Cells; T-Lymphocytes, Regulatory; Kidney Transplantation; Graft Rejection; Mice, Inbred BALB C; Mice; Mice, Inbred C57BL; Chromones; Male; Immunosuppressive Agents; Humans; Cell Differentiation; Disease Models, Animal; Cells, Cultured; Sulfonamides
PubMed: 38850789
DOI: 10.1016/j.intimp.2024.112409